Naïve CD4+ cells from MS patients had higher NF-κB phospho-p65 than those from HC; MS risk variant rs228614 near NF-κB1 was associated with increased NF-κB signaling; rs1800693 in TNFR1 was associated with enhanced NF-κB responses to TNF-α and plasma cytokines. Here, TNF is linked to myeloid sarcoma.